PracticeUpdate Conference Series ISN WCN 2019

SONAR Study Reveals Potential for Atrasentan to Slow Kidney Disease Progression in Well-Selected Patients Trial is an important example of precisionmedicine.

T he investigational endothelin inhibitor atrasentan shows promise for slowing the pro- gression of kidney disease among patients with type 2 diabetes and diabetic nephropathy, provided they are preselected for good response rate and lack of fluid retention. These are the main findings of the atrasentan and renal events in type 2 diabetes with chronic kid- ney disease Study Of diabetic Nephropathy with atrasentan (SONAR) trial, presented for the first time at WCN 2019. The study authors emphasized that this trial is an example of the future of preci- sion medicine, in which therapies are tailored to individual patients. Endothelin has multiple pathophysiological effects that contribute to the progression of chronic kidney disease. Previous studies of endothelin antagonists among patients with diabetes revealed a reduction in albuminuria but also a potential increase in fluid reten- tion, which could contribute to heart failure. Clinical findings, however, do suggest that, in selected patients, atrasentan can be dosed to provide ben- eficial effects with a minimal risk of adverse events. SONAR was a predictive enrichment trial, mean- ing it was designed to maximize the benefits of and minimize the adverse events of atrasentan by identifying patients who respond to the drug with reduced albuminuria and without weight gain. The rationale, study design, results and clinical implications of the trial were each presented at WCN by separate members of the SONAR Steering Committee.

One of these members is Ricardo Correa-Rotter, MD, of the National Medical Sciences and Nutrition Institute Salvador Zubirán in Mexico City, Mexico. He told the audience that, “Diabetes is a grow- ing problem. … We are now facing a worldwide epidemic in which, by the year 2040, more than 600 million people will be diabetic. And of those who are diabetic, at least 1 in 3 will have diabetic kidney disease. As nephrologists, we have to acknowledge that sometimes we underplay the prognosis of the diabetic patient on dialysis.” He pointed out that the 5-year survival is poorer than for prostate cancer, breast cancer, thyroid cancer, Hodgkin’s lymphoma, and several other serious neoplastic diseases. Inclusion criteria for the SONAR trial included an esti- mated glomerular filtration rate (eGFR) 25 to 75 mL/ min/1.73 m 2 , a urinary albumin-to-creatinine ratio (UACR) between 300mg/m and 5000 mg/g, and a brain natriuretic peptide (BNP) level ≤200 pg/mL. For the trial, 11,087 adult patients with type 2 diabe- tes and diabetic nephropathy were recruited for a 14-day screening period. From there, 5360 of the eligible patients entered a run-in period that was 2 weeks long if they were receiving the maximum dose of a renin-angiotensin system (RAS) inhib- itor or 4 to 12 weeks if they were not. Next, 5117 patients entered the enrichment period, in which they received atrasentan 0.75 mg daily for 6 weeks in an open-label fashion. Those who gained >3kg or developed BNP >300 pg/mL or heart failure stopped therapy and left the trial.

Dr. Ricardo Correa-Rotter

PRACTICEUPDATE CONFERENCE SERIES • WCN 2019 10